1. Field of the Invention
The invention generally relates to novel acylcarnitine analogues and their use as topical, microbicidal spermicides. The acylcarnitine analogues are excellent spermicides, growth inhibitors of Candida albicans, and anti-HIV agents.
2. Background of the Invention
Many women want to control their fertility and reduce their risk of becoming infected with a sexually transmitted disease (STD). The AIDS epidemic has intensified the need for female-controlled methods that provide effective protection against both pregnancy and STDs (Irwin et al. 1998). No currently available agent simultaneously protects against both pregnancy and infection. There is a need to develop safe prophylactic agents that are spermicidal and display activity against HIV and STD pathogens.
Nonoxynol-9 (N-9), a nonionic surfactant, is the most widely used spermicides in the United States. Unfortunately, it does not appear to reduce the incidence of HIV infection (Rowe, 1997; Hira et al. 1997; Martin et al., 1997; Roddy et al. 1998). In fact, it has been demonstrated that N-9 actually increases the risk of genital inflammation (Stafford et al., 1998), urinary tract infections (Fihn et al., 1996), vulvovaginal candidiasis (Geiger and Foxman, 1996), and genital ulcers (Feldblum. 1996). One Canadian province no longer recommends the use of N-9 in any form (Rekart, 1992). Furthermore, N-9 is a mixture of oligomers (Yu and Chien, 1995) which may not meet future regulations as the health-care industry moves toward using pure compounds or mixtures whose individual components have met safety standards. For reasons of environmental toxicity (Thiele et al. 1997), several European nations have banned or restricted the use of N-9 and related compounds, sparking a debate (Renner, 1997) about the health risks of N-9. Clearly, other alternatives to N-9 as a microbicidal spermicide are needed.
It would be of benefit to have available an agent which displayed both spermicidal and anti-STD properties, particularly if the agent was non-irritating and did not increase the risk of inflammation and infection. It would be especially of benefit if the agent was active against the devastating disease of AIDS.
It is an object of this invention to provide acylcarnitine analogues of the general formula 
wherein R is an alkyl chain having 10-30 carbons. In the preferred embodiment R is selected from the group consisting of xe2x80x94C10H21, xe2x80x94C11H23, xe2x80x94C12H25, xe2x80x94C13H27, xe2x80x94C14H29, xe2x80x94C16H33, xe2x80x94C17H35, xe2x80x94C18H37, xe2x80x94C19H39, xe2x80x94C20H41, xe2x80x94C21H43 and xe2x80x94C22H45.
It is a further object of the instant invention to provide a composition of matter comprising a carrier and an acylcarnitine analogue of the general formula depicted in Formula 1 wherein R is an alkyl chain selected from the group consisting of xe2x80x94C10H21 to xe2x80x94C30H61, and where R is preferably xe2x80x94C10H21 to xe2x80x94C22H45. The composition of matter may further comprise an acid. In a preferred embodiment, the acid is mucic acid. The carrier may be a gel.
The instant invention also provides a method of contraception for a female mammal. In a preferred embodiment, a contraceptively effective amount of a microbicidal spermicide comprising an acylcarnitine analogue as depicted in Formula 1, wherein R is an alkyl chain selected from the group consisting of xe2x80x94C10H21 to xe2x80x94C30H61, is placed in the vaginal cavity of the female mammal. The microbicidal spermicide may be a gel, and may further comprise an acid such as mucic acid.
The present invention also provides a method of inactivating mammalian spermatozoa, comprising contacting the spermatozoa with a spermicidally effective amount of a compound comprising an acylcarnitine analogue of the general formula depicted in Formula 1, wherein R is an alkyl chain selected from the group consisting of xe2x80x94C10H21 to xe2x80x94C30H61. In a preferred embodiment, R=xe2x80x94C10H21 to xe2x80x94C22H45. The compound may be a gel, and may further comprise an acid such as mucic acid.
The present invention also provides a method of neutralizing human immunodeficiency virus, comprising contacting a human immunodeficiency virus with an effective amount of a compound comprising an acylcarnitine analogue of the general formula depicted in Formula 1, wherein R is an alkyl chain selected from the group consisting of xe2x80x94C10H21 to xe2x80x94C30H61. In a preferred embodiment, R=xe2x80x94C10H21 to xe2x80x94C22H45. The compound may be a gel, and may further comprise an acid such as mucic acid.
The present invention also provides a method of inhibiting growth of Candida albicans, comprising contacting Candida albicans with an effective amount of a compound comprising an acylcarnitine analogue of the general formula depicted in Formula 1, wherein R is an alkyl chain selected from the group consisting of xe2x80x94C10H21 to xe2x80x94C30H61. In a preferred embodiment, R=xe2x80x94C10H21 to xe2x80x94C22H45. The compound may be a gel, and may further comprise an acid such as mucic acid.
The present invention also provides a method for simultaneously inactivating mammalian spermatozoa, neutralizing human immunodeficiency virus, and inhibiting growth of Candida albicans in a female mammal in need thereof, comprising administering intravaginally to a female mammal a quantity of a microbicidal spermicide sufficient to inactivate mammalian spermatozoa, neutralize human immunodeficiency virus, and inhibit growth of Candida albicans in said female mammal. The microbicidal spermicide comprises an acylcamitine analogue of the general formula depicted in Formula 1, wherein R is an alkyl chain selected from the group consisting of xe2x80x94C10H21 to xe2x80x94C30H61. In a preferred embodiment, R=xe2x80x94C10H21 to xe2x80x94C22H45. The compound may be a gel, and may further comprise an acid such as mucic acid.